3,5-Dimethoxyamphetamine

{{Infobox drug

| drug_name =

| image = 3,5-Dimethoxyamphetamine.svg

| width =

| caption =

| pronounce =

| tradename =

| Drugs.com =

| MedlinePlus =

| licence_CA =

| licence_EU =

| DailyMedID =

| licence_US =

| pregnancy_AU =

| pregnancy_category =

| dependency_liability =

| addiction_liability =

| routes_of_administration =

| class =

| ATC_prefix =

| ATC_suffix =

| legal_status =

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

| CAS_number = 15402-82-1

| CAS_supplemental =

| PubChem = 91247

| PubChemSubstance =

| IUPHAR_ligand =

| DrugBank =

| ChemSpiderID = 82397

| UNII = 4U6LN22RX4

| KEGG =

| ChEBI =

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = 3,5-DMA; DMA-6

| IUPAC_name = 1-(3,5-dimethoxyphenyl)propan-2-amine

| C=11 | H=17 | N=1 | O=2

| SMILES = CC(CC1=CC(=CC(=C1)OC)OC)N

| StdInChI = 1S/C11H17NO2/c1-8(12)4-9-5-10(13-2)7-11(6-9)14-3/h5-8H,4,12H2,1-3H3

| StdInChIKey = PDCLPGSYMZLLDX-UHFFFAOYSA-N

}}

3,5-Dimethoxyamphetamine (3,5-DMA), also known as DMA-6, is a drug of the amphetamine family and a positional isomer of dimethoxyamphetamine (DMA).{{cite book | vauthors = Shulgin A, Manning T, Daley PF | chapter = #39. 3,5-DMA | pages = 70–71 | chapter-url = https://archive.org/details/shulgin-index-vol-1/page/70/mode/1up | title = The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher = Transform Press | location = Berkeley, CA | volume = 1 | year = 2011 | isbn = 978-0-9630096-3-0 | oclc = 709667010 }} It is the parent structure of the 3C (4-substituted 3,5-dimethoxyamphetamine) family of compounds (also known as 3C-scalines).

In an early study, it showed similar affinity for serotonin receptors as mescaline (3,4,5-trimethoxyphenethylamine) but had more than an order of magnitude lower affinity than DOx (4-substituted 2,5-dimethoxyamphetamine) drugs like DOM, DOET, and DOB.{{cite journal | vauthors = Glennon RA, Liebowitz SM, Anderson GM | title = Serotonin receptor affinities of psychoactive phenalkylamine analogues | journal = J Med Chem | volume = 23 | issue = 3 | pages = 294–299 | date = March 1980 | pmid = 7365744 | doi = 10.1021/jm00177a017 | url = https://www.erowid.org/archive/rhodium/pdf/glennon.pea.receptor.affinities.pdf}} However, in a later study, it showed no or very low affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = >10,000{{nbsp}}nM), whereas DOB showed high affinity for these receptors (K_i = 32{{nbsp}}nM and 64{{nbsp}}nM, respectively).{{cite journal | vauthors = Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA | title = 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists | journal = J Med Chem | volume = 43 | issue = 16 | pages = 3074–3084 | date = August 2000 | pmid = 10956215 | doi = 10.1021/jm9906062 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ad45346022bb7e6e1bec1fbfbcca3bcb60b13058| url-access = subscription }} 3,5-DMA's effects on monoamine reuptake and efflux have also been studied. It appeared to be weak or inactive as a norepinephrine reuptake inhibitor and norepinephrine releasing agent.{{cite journal | vauthors = Benington F, Morin RD | title = The chemorelease of norepinephrine from mouse hearts by substituted amphetamines | journal = J Med Chem | volume = 11 | issue = 4 | pages = 896–897 | date = July 1968 | pmid = 5677681 | doi = 10.1021/jm00310a048 | url = }}{{cite journal | vauthors = Paton DM | title = Effect of amphetamine, 3,4-methylenedioxyamphetamine, p-methoxyamphetamine and related amphetamines on uptake of metaraminol and efflux of noradrenaline in adrenergic nerves of rabbit atria | journal = J Pharm Pharmacol | volume = 27 | issue = 5 | pages = 361–362 | date = May 1975 | pmid = 239139 | doi = 10.1111/j.2042-7158.1975.tb09456.x | url = }} Likewise, it was a very weak serotonin reuptake inhibitor ({{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} = 18,500{{nbsp}}nM) and serotonin releasing agent (active at ≥10,000{{nbsp}}nM).{{cite journal | vauthors = Tseng LF, Loh HH | title = Effects of methoxyamphetamines on the uptake and release of [3H]5-hydroxytryptamine by human blood platelets | journal = Biochem Pharmacol | volume = 26 | issue = 7 | pages = 647–649 | date = April 1977 | pmid = 577148 | doi = 10.1016/0006-2952(77)90041-7 | url = }}

3,5-DMA was inactive in substituting for DOM in rodent drug discrimination tests (4–14% appropriate responding for 5–12.5{{nbsp}}mg/kg), suggesting that it would not be hallucinogenic in humans.{{cite journal | vauthors = Glennon RA, Young R | title = Comparison of behavioral properties of di- and tri-methoxyphenylisopropylamines | journal = Pharmacol Biochem Behav | volume = 17 | issue = 4 | pages = 603–607 | date = October 1982 | pmid = 6965276 | doi = 10.1016/0091-3057(82)90330-6 | url = }} However, it has shown other pharmacological effects in mice and with similar potency as mescaline, whereas it was inactive in rats.{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Phenylalkylamines and Their Derivatives | pages = 55–97 | title = Hallucinogenic Agents | date = 1975 | location = Bristol | publisher = Wright-Scientechnica | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1#page=33 }} The effects of 3,5-DMA in humans have not been reported. 3,5-DMA has been detected as an adulterant in forensic drug samples.{{cite journal | vauthors = Giné CV, Espinosa IF, Vilamala MV | title = New psychoactive substances as adulterants of controlled drugs. A worrying phenomenon? | journal = Drug Test Anal | volume = 6 | issue = 7–8 | pages = 819–24 | date = 2014 | pmid = 24470121 | doi = 10.1002/dta.1610 | url = }} As a positional isomer of 2,5-dimethoxyamphetamine (2,5-DMA; DMA-4), 3,5-DMA is a Schedule I controlled substance in the United States.

A derivative of 3,5-DMA, 4-bromo-3,5-dimethoxyamphetamine (4-Br-3,5-DMA), showed relatively high affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = 210{{nbsp}}nM and 570{{nbsp}}nM, respectively). However, it was not active as a psychedelic at the assessed doses (4–10{{nbsp}}mg).{{cite web |url=http://www.erowid.org/library/books_online/pihkal/pihkal018.shtml |title=4-Bromo-3,5-dimethoxyamphetamine Entry in PiHKAL |access-date=2007-03-28 |archive-date=2007-06-06 |archive-url=https://web.archive.org/web/20070606132613/http://erowid.org/library/books_online/pihkal/pihkal018.shtml |url-status=live }}